Comparative Efficacy of Different Mebendazole Polymorphs in the Treatment of Soil-transmitted Helminth Infections

NCT ID: NCT01350271

Last Updated: 2013-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2011-06-30

Brief Summary

Mebendazole tablets which are produced by most pharmaceutical manufacturers, including the State Pharmaceutical Manufacturing Corporation (SPMC) of Sri Lanka, contain a mixture of polymorphs A and C. However, there is some evidence to show that mebendazole polymorph C is the only form effective against the soil-transmitted helminths. This protocol describes a stratified, randomized, placebo-controlled trial that examined the efficacy of different mebendazole polymorphs produced by the SPMC in the treatment of hookworm infections.

Detailed Description

Mebendazole has three polymorphic forms, identified as A, B and C. All of them are in accord with the US Pharmacopeia specifications (USP XXI) but they have distinct physiochemical characteristics (Himmelreich et al, 1977) and different therapeutic activities in experimentally infected mice with Trichinella spiralis infections (Rodriguez-Caabeiro et al, 1987). The original mebendazole tablets which were used to treat human infections had more than 90% of polymorph C (Van den Bossche et al, 1982), but most pharmacopeias currently do not specify the proportion of polymorph C that a tablet of mebendazole should contain, and the assay specified for measurement of the active ingredient measures all polymorphs together. There is some evidence to show that unlike polymorph C, polymorph A is ineffective in the treatment of hookworm and whipworm infections (Charoenlarp et al, 1993). The State Pharmaceutical Manufacturing Corporation of Sri Lanka produces both 500 mg and 100 mg tablets of mebendazole according to specifications laid down in the US Pharmacopeia. These tablets contain a mixture of polymorphs A and C. It is possible that increasing the content of mebendazole polymorph C in single dose tablets may improve cure rates and egg reduction rates, especially against hookworm and whipworm infections, where much variation in efficacy has been observed.

Conditions

Necator Americanus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka

Mebendazole polymorph A and C 500 mg

Mebendazole tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg of mebendazole as a 50:50 mixture of Polymorphs A and C

Group Type: ACTIVE_COMPARATOR

Mebendazole polymorph A and C 500 mg

Intervention Type: DRUG

Mebendazole tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg of mebendazole as a 50:50 mixture of Polymorphs A and C

Mebendazole polymorph C 500 mg

Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone

Group Type: EXPERIMENTAL

Mebendazole polymorph C

Intervention Type: DRUG

Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone

Interventions

Mebendazole polymorph A and C 500 mg

Mebendazole tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg of mebendazole as a 50:50 mixture of Polymorphs A and C

Intervention Type: DRUG

Mebendazole polymorph C

Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone

Intervention Type: DRUG

Placebo

Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka

Intervention Type: DRUG

Other Intervention Names

Lot FG10M01; Lot FG10H01

Eligibility Criteria

Inclusion Criteria

• Necator americanus infection, as determined by examination of a single faecal smear, alone or with Ascaris lumbricoides or Trichuris trichiura

Exclusion Criteria

• Children below the age of 2 years
• Pregnant women
• Individuals with diarrhea on day of treatment

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kelaniya

OTHER

Sponsor Role: lead

Responsible Party

N R de Silva

Professor of Parasitology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nilanthi R de Silva, MD

Role: PRINCIPAL_INVESTIGATOR

Faculty of Medicine, University of Kelaniya, Sri Lanka

Locations

Lellopitiya Estate, Hapugastenne Plantations PLC

Ratnapura, Sabragamuwa, Sri Lanka

Agalawatta Plantations PLC

Nivithigala, Sabragamuwa, Sri Lanka

Countries

Sri Lanka

Other Identifiers

Ragama ERC

Identifier Type: REGISTRY

Identifier Source: secondary_id

P39/04/2010

Identifier Type: -

Identifier Source: org_study_id